The long range objective of this research proposal is to study the hepatic process of gluconeogenesis in vivo, that is, in the dog and ultimately in intact man. Specifically, we wish to: 1) determine the contribution of circulating alanine to hepatic glucose production in the fed, postabsorptive, and prolonged fasted states; 2) define the physiological roles of insulin and glucagon in the regulation of gluconeogenesis from alanine; and 3) study the pathophysiology of the accelerated gluconeogenesis of diabetic man. To date, our studies have involved the first two objectives. In normal man, using the hepatic vein catheterization technique combined with a constant infusion of alanine-14C, we have examined the effects of fasting 12 and 48 hours and 3 weeks. Using somatostatin, we have also examined the roles of basal insulin and glucagon in regulating basal gluconeogenesis in the dog. In the next year we plan to examine the roles of insulin and glucagon in intact man in regulating gluconeogenesis from alanine. We will use somatostatin as a means of producing isolated deficiencies of insulin and glucagon. We will examine the role of glucose (independent of insulin) in regulating gluconeogenesis. We have noted in human studies that the glycogenolytic effect of glucagon is short-lived while its stimulatory effects on gluconeogenesis are much more prolonged, a phenomenon we plan to further investigate. BIBLIOGRAPHIC REFERENCES: Chiasson, J.L., Liljenquist, J.E., Sinclair-Smith, B.C. and Lacy, W.W. Gluconeogenesis from alanine in normal postabsorptive man. Intrahepatic stimulatory effect of glucagon. Diabetes, 24:574-584, 1975. Liljenquist, J.E., Chiasson, J.L., Jennings, A.S., Horwitz, D.L. and Rubenstein, A.H. Insulin Suppression of Insulin Secretion in man. Diabetes 24 (suppl. 2) 44, 1975. (Abstract).